TARGETED DISRUPTION OF THE LOW-AFFINITY LEUKEMIA INHIBITORY FACTOR-RECEPTOR GENE CAUSES PLACENTAL, SKELETAL, NEURAL AND METABOLIC DEFECTS AND RESULTS IN PERINATAL DEATH

The low-affinity receptor for leukemia inhibitory factor (LIFR) inter acts with gp130 to induce an intracellular signal cascade, The LIFR-gp 130 heterodimer is implicated in the function of diverse systems, Norm al placentation is disrupted in LIFR mutant animals, which leads to po or intrauterine nutrition but allows fetuses to continue to term. Feta l bone volume is reduced greater than three-fold and the number of ost eoclasts is increased six-fold, resulting in severe osteopenia of peri natal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of g lycogen, indicating a metabolic disorder. Hematologic and primordial g erm cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth.